Stem Cell Reports最新文献_第6页

Genetic Engineering of Human Embryonic Stem Cells for Precise Cell Fate Tracing during Human Lineage Development. 人类胚胎干细胞基因工程用于人类谱系发育过程中细胞命运的精确追踪。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-08-11 Epub Date: 2026-07-30 DOI: 10.1016/j.stemcr.2026.103054

Zhenyu Chen, Xudong Ren, Xiangjie Xu, Xiaojie Zhang, Yi Hui, Zhongliang Liu, Lei Shi, Yujiang Fang, Lin Ma, Yang Liu, Daniel Terheyden-Keighley, Ling Liu, Xiaoqing Zhang

引用次数: 0

CCL5 exposure promotes acute and transient megakaryopoiesis and hematopoietic progenitor expansion. CCL5暴露促进急性和短暂巨核生成和造血祖细胞扩增。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-08-11 Epub Date: 2026-07-16 DOI: 10.1016/j.stemcr.2026.103014

Maria N Barrachina, Dong H Lee, Virginia Camacho, Karen G Wang, Ethan Walsey, Estelle Carminita, Isabelle C Becker, Siobhan Branfield, Daniela Freire, Emma Nikols, Emma L Berdan, Blen Yohannes, Olivera Miladinovic, Julia Tilburg, Joseph E Italiano, Kellie R Machlus

{"title":"CCL5 exposure promotes acute and transient megakaryopoiesis and hematopoietic progenitor expansion.","authors":"Maria N Barrachina, Dong H Lee, Virginia Camacho, Karen G Wang, Ethan Walsey, Estelle Carminita, Isabelle C Becker, Siobhan Branfield, Daniela Freire, Emma Nikols, Emma L Berdan, Blen Yohannes, Olivera Miladinovic, Julia Tilburg, Joseph E Italiano, Kellie R Machlus","doi":"10.1016/j.stemcr.2026.103014","DOIUrl":"10.1016/j.stemcr.2026.103014","url":null,"abstract":"During inflammation, megakaryocytes (MKs) can expand from hematopoietic stem cells, yet the specific driving factors remain unclear. We investigated whether C-C Motif Chemokine Ligand 5 (CCL5) influences this process in murine and human iPSC-derived bone marrow organoid (BMO) models. Acute CCL5 administration to mice increased hematopoietic stem and progenitor cell (HSPC) populations and increased MKs, including the expansion of MHC II-expressing MKs, characteristic of the immune MK subpopulation. Mechanistically, MK progenitors upregulated CCR1 and CCR5, and MKs showed increased phosphorylation of JAK1, SRC, and STAT1-5. Phenotypically, transcriptomic profiling revealed enhanced expression of genes associated with the cell cycle, inflammatory pathways, and mitochondrial metabolism in MKs isolated from CCL5-treated mice, which was functionally supported by increased mitochondrial activity. Similarly, in human BMOs, CCL5 treatment increased MK numbers. Together, these findings implicate CCL5 as a direct mediator of acute megakaryopoiesis and immune MK expansion during inflammation.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103014"},"PeriodicalIF":5.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GLP-1 regulates osteo-adipogenic fate of BMSCs via HIF-2-AKT signaling and supports trabecular bone in glucocorticoid-induced osteoporosis. GLP-1通过HIF-2-AKT信号调节骨髓间充质干细胞的成脂命运，并在糖皮质激素诱导的骨质疏松症中支持骨小梁。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-08-11 Epub Date: 2026-07-09 DOI: 10.1016/j.stemcr.2026.103008

Zhe Yang, Xin Li, Niujian Wu, Ling Wang, Zhanjin Lu, Lingling Wang, Shisong Han, Hongyun Lu

{"title":"GLP-1 regulates osteo-adipogenic fate of BMSCs via HIF-2-AKT signaling and supports trabecular bone in glucocorticoid-induced osteoporosis.","authors":"Zhe Yang, Xin Li, Niujian Wu, Ling Wang, Zhanjin Lu, Lingling Wang, Shisong Han, Hongyun Lu","doi":"10.1016/j.stemcr.2026.103008","DOIUrl":"10.1016/j.stemcr.2026.103008","url":null,"abstract":"Bone marrow mesenchymal stem cell (BMSC) lineage commitment contributes to metabolic bone diseases, but whether glucagon-like peptide-1 (GLP-1) regulates osteo-adipogenic fate remains unclear. Here, RNA sequencing was performed to identify potential pathways regulated by GLP-1 in BMSCs, followed by gain- and loss-of-function experiments. Furthermore, BMSC-specific Hif-2α knockout mice with glucocorticoid-induced osteoporosis were treated with semaglutide to evaluate skeletal effects. GLP-1 suppressed adipogenesis and promoted osteogenesis of BMSCs in a dose-dependent manner. Transcriptomic analysis identified PI3K-AKT and hypoxia signaling as major GLP-1-regulated pathways. Mechanistically, GLP-1 inhibited AKT activation during adipogenesis and reshaped AKT signaling dynamics during osteogenesis. Loss of HIF-2α largely abolished GLP-1-mediated regulation of AKT activity. In vivo, semaglutide improved trabecular bone mass in osteoporotic mice, whereas this bone-protective effect was markedly diminished in Hif-2α-knockout mice. Our findings suggest that GLP-1 modulates BMSC lineage commitment by inhibiting adipogenesis and enhancing osteogenesis through HIF-2α-associated regulation of AKT signaling.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103008"},"PeriodicalIF":5.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PRDM16 modulates aspects of cell cycle dynamics and maturation in human iPSC-derived cardiomyocytes. PRDM16调节人类ipsc衍生的心肌细胞的细胞周期动力学和成熟方面。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-08-11 Epub Date: 2026-07-09 DOI: 10.1016/j.stemcr.2026.103005

Kanae Tani, Yasuko Matsumura, Misato Nishikawa, Megumi Narita, Amanda Putri Elvandari, Antonio Lucena-Cacace, Yoshinori Yoshida

{"title":"PRDM16 modulates aspects of cell cycle dynamics and maturation in human iPSC-derived cardiomyocytes.","authors":"Kanae Tani, Yasuko Matsumura, Misato Nishikawa, Megumi Narita, Amanda Putri Elvandari, Antonio Lucena-Cacace, Yoshinori Yoshida","doi":"10.1016/j.stemcr.2026.103005","DOIUrl":"10.1016/j.stemcr.2026.103005","url":null,"abstract":"Deciphering how cardiomyocytes exit proliferation and acquire postnatal maturity is essential for understanding heart development and regenerative potential. We identify PRDM16 as a regulator that influences the balance between proliferation and maturation in human iPSC-derived cardiomyocytes (hiPSC-CMs). Mechanistically, PRDM16 controls proliferative activity by modulating CDK1 and phospho-AKT, two central drivers of cardiomyocyte cell cycle progression. Loss of PRDM16 profoundly disrupts metabolic and structural maturation, yielding abnormal sarcomeric protein ratios and impaired engineered heart tissue function. In contrast, moderate PRDM16 overexpression promotes metabolic rewiring and structural remodeling characteristic of mature cardiomyocytes. These findings support a model in which PRDM16 functions as a context-dependent modulator governing the transition from proliferation to maturation. By demonstrating that transient downregulation favors proliferation while sustained expression drives maturation, our work highlights PRDM16 as both a potential developmental regulator and a therapeutic target for enhancing cardiomyocyte regeneration, cardiac repair, and the functional engineering of human heart tissues.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103005"},"PeriodicalIF":5.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single cell CRISPR screen identifies antagonism between Nsd1-H3K36me2 and Ezh2-H3K27me3 orchestrates pluripotency transition. 单细胞CRISPR筛选发现Nsd1-H3K36me2和Ezh2-H3K27me3之间的拮抗作用协调多能性转变。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-08-11 Epub Date: 2026-07-16 DOI: 10.1016/j.stemcr.2026.103016

Yuqing Zhu, Qingying Wang, Yanzi Cao, Linxiao Hou, Lin Yang, Chen Cheng, Shoudong Ye, Wei Li, Jin Zhang

{"title":"Single cell CRISPR screen identifies antagonism between Nsd1-H3K36me2 and Ezh2-H3K27me3 orchestrates pluripotency transition.","authors":"Yuqing Zhu, Qingying Wang, Yanzi Cao, Linxiao Hou, Lin Yang, Chen Cheng, Shoudong Ye, Wei Li, Jin Zhang","doi":"10.1016/j.stemcr.2026.103016","DOIUrl":"10.1016/j.stemcr.2026.103016","url":null,"abstract":"The transcriptional and epigenetic landscape imposes constraints on the self-renewal capacity and lineage specification potential of both naive and primed mouse embryonic stem cells (mESCs). CRISPR/Cas9-based functional screening coupled with single-cell RNA-seq (CROP-seq) establishes relationships between gRNA-mediated knockout genotype and transcriptome phenotype, providing a powerful tool to dissect gene regulatory networks. Here, we employed CROP-seq to investigate the epigenetic regulation governing the pluripotency network in mESCs. This highly sensitive method identified key genes essential for the acquisition and exit from pluripotency, and revealed a novel role for H3K36me2 in modulating DNA methylation through regulating the expression of Dnmt1 and Dnmt3a. Specifically, loss of Nsd1-mediated H3K36me2 delayed naive state exit, whereas Ezh2 deficiency accelerated primed entry. Collectively, our findings identify an epigenetic regulatory network critical for determining mESCs' pluripotent state transitions.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103016"},"PeriodicalIF":5.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Brain injury reactivates a developmental program driving genesis and integration of transient LGE-class interneurons. 脑损伤重新激活了一个发育程序，驱动瞬态大鼠级中间神经元的发生和整合。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-08-11 Epub Date: 2026-07-16 DOI: 10.1016/j.stemcr.2026.103015

G Nato, M Fogli, N Marichal, V Cerrato, G Turrini, V Proserpio, I Ghia, G Zanotto, I Molineris, M Bergami, S Oliviero, P Peretto, B Berninger, A Buffo, F Luzzati

{"title":"Brain injury reactivates a developmental program driving genesis and integration of transient LGE-class interneurons.","authors":"G Nato, M Fogli, N Marichal, V Cerrato, G Turrini, V Proserpio, I Ghia, G Zanotto, I Molineris, M Bergami, S Oliviero, P Peretto, B Berninger, A Buffo, F Luzzati","doi":"10.1016/j.stemcr.2026.103015","DOIUrl":"10.1016/j.stemcr.2026.103015","url":null,"abstract":"Brain lesions can unlock latent neurogenic potential in parenchymal astrocytes, but the identity of their neuronal progeny has remained unclear. Here, we show that neurons generated by striatal astrocytes after excitotoxic lesions are transient, yet reach advanced morphological and functional maturation and integrate into cortico-striatal-thalamic circuits. Single-cell RNA-seq mapping onto an embryonic reference revealed these cells are not fated to adult striatal neuron types but belong to the LGE-MEIS2/PAX6 interneuron class. Reanalysis of neuroblasts from cortical and striatal astrocytes after Notch abrogation revealed shared commitment of rostral telencephalic astrocytes to this class. Public spatial transcriptomics datasets revealed these cells are widely distributed throughout the mouse telencephalon during embryonic and postnatal development. Thus, unlike other vertebrates in which adult telencephalic astroglia preserve the potential to generate resident, regionally appropriate neuronal types, homologous mammalian cells converge on a specific transient neuron class, possibly representing a reservoir for circuit plasticity in adult life.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103015"},"PeriodicalIF":5.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148472836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of gastric cancer patient-derived organoids in precision medicine: Clinicians' perspective. 胃癌患者源性类器官在精准医学中的作用：临床医生的观点。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-08-11 Epub Date: 2026-07-09 DOI: 10.1016/j.stemcr.2026.103006

Tharindie N Silva, Harleen Kaur, Tharani Krishnan, David S Liu, Margaret Lee, Markus Trochsler, Nicholas J Clemons, Josephine A Wright, Susan L Woods

{"title":"The role of gastric cancer patient-derived organoids in precision medicine: Clinicians' perspective.","authors":"Tharindie N Silva, Harleen Kaur, Tharani Krishnan, David S Liu, Margaret Lee, Markus Trochsler, Nicholas J Clemons, Josephine A Wright, Susan L Woods","doi":"10.1016/j.stemcr.2026.103006","DOIUrl":"10.1016/j.stemcr.2026.103006","url":null,"abstract":"Organoid technology holds great potential and hope for personalized treatment in gastric cancer (GC). To date, clinicians' views on this technology for precision oncology have not been reported despite these insights being invaluable to understanding how organoids may be effectively integrated into clinical practice. Hence, we explored clinicians' knowledge and perception of organoid research and its potential clinical utility in GC treatment. Clinicians believed that organoids would be most useful for guiding adjuvant treatment in patients who fail neoadjuvant therapy and emphasized the importance of obtaining results within 4-6 weeks of surgical resection. Clinicians also expressed concerns and suggestions related to current research methodologies and highlighted the ethical and political aspects of organoid-guided personalized medicine. Overall, most clinicians perceived the value in the use of organoids to guide personalized treatment in GC and provided important insights into how this approach could be best implemented in clinical practice in the future.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103006"},"PeriodicalIF":5.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Induction of human pruriceptors from pluripotent stem cells via transcription factors. 通过转录因子从多能干细胞诱导人受体。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-08-11 Epub Date: 2026-07-09 DOI: 10.1016/j.stemcr.2026.103004

Hisato Iriki, Ruiqi Hu, Xu Li, Erdene Baljinnyam, Carina Habich, Ichiro Imanishi, Loan N Miller, Kavya Chegireddy, Laraib Iqbal Malik, Daniel Yassky, Raphael Kübler, Aaron Ver Heul, Kathleen M Smith, Peter Reinhardt, Eric R Goedken, Brian S Kim, Samuele G Marro

{"title":"Induction of human pruriceptors from pluripotent stem cells via transcription factors.","authors":"Hisato Iriki, Ruiqi Hu, Xu Li, Erdene Baljinnyam, Carina Habich, Ichiro Imanishi, Loan N Miller, Kavya Chegireddy, Laraib Iqbal Malik, Daniel Yassky, Raphael Kübler, Aaron Ver Heul, Kathleen M Smith, Peter Reinhardt, Eric R Goedken, Brian S Kim, Samuele G Marro","doi":"10.1016/j.stemcr.2026.103004","DOIUrl":"10.1016/j.stemcr.2026.103004","url":null,"abstract":"Pruriception is crucial for defense against external stimuli but can lead to chronic pruritus, a debilitating condition affecting millions worldwide. Our understanding of the cellular and molecular mechanisms behind the sensation of itch has been hindered by the lack of functional human models. Here, we address this limitation by developing a protocol to generate induced pruriceptors (iPruriceptors) from human-induced pluripotent stem cells (iPSCs). We compared two differentiation approaches: a direct method via forced expression of transcription factors (TFs) in iPSCs and a 2-step process through expression of TFs in iPSC-derived neural crest cells (NCCs). The 2-step protocol proved superior in inducing a transcriptional program enriched for features of human pruriceptors. Our optimized protocol employs forced expression of NGN1 and ISL1 to drive differentiation from NCCs into pruriceptors, enhancing the expression of known pruritogen receptors such as IL31RA, which pairs with OSMR, and HRH1. The induction of this transcriptional program leads to functional maturation of iPruriceptors. Accordingly, iPruriceptors exhibit robust responses to itch stimuli and in vivo-like itch pharmacology such as treatment with ABT-317, a JAK1 inhibitor tool compound, similar to those targeting intensive pruritus in atopic dermatitis (AD). Importantly, iPruriceptors can be generated without viral vectors or safe-harbor gene editing, using a PiggyBac-based transfection method that simplifies scalability. Our protocol offers a robust platform for investigating itch biology, modeling chronic pruritus, and enabling high-throughput screening for therapeutic target discovery.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103004"},"PeriodicalIF":5.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In silico optimization of regenerative cell therapy in the infarcted human ventricles to mitigate arrhythmic burden. 用计算机优化再生细胞治疗梗死心室以减轻心律失常负担。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-08-11 Epub Date: 2026-07-09 DOI: 10.1016/j.stemcr.2026.103007

Leto Luana Riebel, Zhinuo Jenny Wang, Xin Zhou, Lucas Arantes Berg, Cristian Trovato, Blanca Rodriguez

{"title":"In silico optimization of regenerative cell therapy in the infarcted human ventricles to mitigate arrhythmic burden.","authors":"Leto Luana Riebel, Zhinuo Jenny Wang, Xin Zhou, Lucas Arantes Berg, Cristian Trovato, Blanca Rodriguez","doi":"10.1016/j.stemcr.2026.103007","DOIUrl":"10.1016/j.stemcr.2026.103007","url":null,"abstract":"Myocardial infarction remains a frequent cause of heart failure and mortality. Cell therapy has shown promise in regenerating the damaged tissue, but delivered cells may beat spontaneously and produce ventricular arrhythmias, hindering clinical application. Here, we conducted multiscale computer simulations of the electrical activity of the infarcted human ventricles including the cardiac conduction system to identify and mitigate pro-arrhythmic mechanisms following cell delivery. Firstly, our simulations show how arrhythmic risk increases from before to after cell injection and further during the first two weeks post-delivery. Secondly, we suggest that concurrently targeting the funny current, the inward rectifier potassium current, the sodium-potassium pump current, and the rapid delayed outward rectifier potassium current may reduce automaticity and re-entry while maximizing calcium transient amplitude and thus contractility. Our study demonstrates how modeling and simulation enables the design of anti-arrhythmic strategies to improve therapy safety while preserving efficacy.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103007"},"PeriodicalIF":5.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148424299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High and intermittent hydrostatic pressure promotes maturation of engineered cardiac tissues derived from human pluripotent stem cells. 高和间歇性静水压力促进人类多能干细胞衍生的工程化心脏组织的成熟。

IF 5.6 2区医学

Stem Cell Reports Pub Date : 2026-08-11 Epub Date: 2026-07-23 DOI: 10.1016/j.stemcr.2026.103019

Wusiman Maihemuti, Kozue Murata, Takahiro Jimba, Jun Iida, Keisuke Hakamada, Akane Sakaguchi, Mosha Abulaiti, Yuichi Saito, Laura Yuriko González-Teshima, Satoshi Takatori, Takahiro Kenmotsu, Kenichi Yoshikawa, Kenji Minatoya, Seitaro Nomura, Wataru Kimura, Hidetoshi Masumoto

{"title":"High and intermittent hydrostatic pressure promotes maturation of engineered cardiac tissues derived from human pluripotent stem cells.","authors":"Wusiman Maihemuti, Kozue Murata, Takahiro Jimba, Jun Iida, Keisuke Hakamada, Akane Sakaguchi, Mosha Abulaiti, Yuichi Saito, Laura Yuriko González-Teshima, Satoshi Takatori, Takahiro Kenmotsu, Kenichi Yoshikawa, Kenji Minatoya, Seitaro Nomura, Wataru Kimura, Hidetoshi Masumoto","doi":"10.1016/j.stemcr.2026.103019","DOIUrl":"10.1016/j.stemcr.2026.103019","url":null,"abstract":"The immaturity of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and engineered cardiac tissues (ECTs) limits their use in regenerative therapies. Ventricular loading pressure plays a vital role in cardiac repair, prompting the hypothesis that hydrostatic pressure could enhance ECT maturation. ECTs were created by co-culturing hPSC-derived cardiovascular cells with extracellular matrix proteins and subjecting them to intermittent hydrostatic pressure (1 h/day at 50 kPa for 3 days after 2 weeks of pre-culture). This protocol improved cardiomyocyte alignment, mitochondrial content, and metabolic and functional maturation, evidenced by enhanced contractility, calcium flux, and single-cell RNA sequencing. Endothelial cells were critical for these effects, as their absence prevented maturation. Hydrostatic pressure combined with dynamic culture also promoted vascular network formation. Transplanted trained ECTs significantly improved ejection fraction in a rat myocardial infarction model. These findings demonstrate the potential of hydrostatic pressure training to advance ECT maturation and therapeutic application.","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"103019"},"PeriodicalIF":5.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0